Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

• 来源期刊: 药学学报（英文版）
• 关键词: Enteric-coated Mycophenolate sodium Mycophenolic acid Nonlinear dynamics Kidney transplantation Pharmacokinetics UPLC-UV Human plasma
• 年，卷（期）: 2017,（3）
• 页码范围: 347-352
• 页数: 6页
• 语种: 英文

摘要

The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients.A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540,720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days.Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration.MPA plasma concentrations were measured by UPLC-UV.The relationship between the EC-MPS dose and its PK parameters was assessed.In the range from 540 to 900 mg,Cmax and AUC0-12h did not increase with dose escalation.The AUC0-12h,Cmax,C0 and Tmax for the 540 720 and 900 mg doses were not significantly different,respectively (P ＞ 0.05).AUC0-12 h and Cmax were increased less than proportionally with increasing EC-MPS dose levels.Inter-individual variability in AUC0-12h,Cmax and Co were considerable.Nonlinear PK relationships were found from the doses of 540-900 mg of EC-MPS.